Restriction mapping of the globin genes from a homozygous δβ thalassemia patient from Israel indicates that at least a 10-kilobase deletion is present extending 3' from within the large intervening sequence (IVS 2) of the δ globin gene and including the entire β globin gene. Unique bands are seen when cellular DNA from this patient is digested with a variety of restriction endonucleases and hybridized with a probe specific for the δ IVS 2. Extensive analysis of the Israeli δβ thalassemia DNA as well as material from an Italian δβ thalassemia homozygote with enzymes which cleave more frequently in δ IVS 2 had localized the 5' end of the deletion to a 107-base pair region within δ IVS 2. This region contains a unique repetitive sequence (TG)4 which has been reported to be a specific recognition signal for recombination and may be involved in the formation of these mutant genes. Two homozygous δ° thalassemia DNA samples from Japan were also analyzed for gene rearrangements or other changes by restriction enzyme mapping. No changes from normal were seen using 14 different enzymes indicating the absence of large deletions in the region around the δ globin gene. More specifically, both the 5' and 3' splice junctions of the IVS 2 appear to be normal from hybridization of restriction fragments generated by HphI and AluI, respectively, with a δ IVS 2 specific probe. We have also shown that point mutations which could lead to termination codons are not present at codons 35, 37, 43, 61, and 121, since restriction enzymes which recognize these sites produce normal patterns. The δ° thalassemia phenotype in these two subjects is most likely due to a point mutation either at one of the other 24 potential termination codons not accessible to restriction analysis or to other single nucleotide changes which could either decrease δ globin gene transcription or lead to abnormal processing or transport of δ globin mRNA.
|Number of pages||4|
|Journal||Journal of Biological Chemistry|
|State||Published - 1984|